PROJECT SUMMARY This is an application for an Administrative Supplement to the Medical Scientist Training Program (MSTP) T32 training grant award. The Need: The goal of the UCSF MSTP is to train the next generation of physician-investigators and equip them with the research and clinical skills they need ?to harness new technologies to advance human health.? However, translation, the process of applying biological insights to clinical problems and vice versa, is difficult and requires unique skills that are not routinely taught in medical school or graduate school. Additional integrative approaches are needed to cultivate these important skills. The Project: We will develop an innovative program for physician-scientist trainees to build skills in ?bedside to bench? and ?bench to bedside? translation through hands-on experience in patient-inspired scientific inquiry. Trainees will work closely with physician-scientist faculty to evaluate patients with rare and unusual phenotypes, with the goal of developing testable hypotheses about the underlying mechanisms of disease. They will then use these hypotheses as a rational framework to propose both patient-centered research studies and biologically grounded recommendations for clinical care. During this process, students will gain valuable experience in relating clinical observations to fundamental scientific principles, interpreting molecular data in light of the appropriate clinical and biological context, and communicating the translational implications of their work to clinical and scientific audiences. In addition, they will complete an embedded curriculum that introduces experimental technologies, e.g. exome sequencing, and bioinformatic tools, e.g. genome browsers, that are useful for studying the molecular basis of human disease. This curriculum will be delivered through online lectures and reinforced with hands-on workshops focused on practical application. Preliminary Experience and Use of Funds: For the past 12 months, we have piloted the program with 12 research-oriented clinical clerkship students, including 7 MSTP students. Their response has been overwhelmingly positive, and they have universally agreed that the program provides a unique opportunity to integrate their clinical and basic science training. If funded, this supplement will provide faculty support to continue the pilot and expand it to include MSTP students in their graduate years, magnifying opportunities for interdisciplinary and team-based learning. In addition, a portion of the funding will be used to create the proposed bioinformatics and technology curriculum, which would not otherwise be possible. Given rapid advances in both the clinical and biological sciences, the process of translation has become both more important and more challenging than ever before. This integrative program is a promising new approach that will prepare physician-scientist trainees for careers in translational research.